Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial.

Acquired hemophilia A (AHA) is a rare but serious bleeding disorder. Randomized controlled trial (RCT) comparing the efficacy of immunosuppression therapy for AHA lacks. We conducted the first multicenter RCT aiming to establish whether the single-dose rituximab combination regimen was noninferior to the cyclophosphamide combination regimen. From 2017 to 2022, 63 patients with newly diagnosed AHA from five centers were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m2 ; n = 31) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks; n = 32). The primary outcome was complete remission (CR, defined as FVIII activity ≥50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 h without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. Twenty-four (77.4%) patients in the rituximab group and 22 (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference = -8.67%, lower limit of the 95% confidence interval = -13.11%; Pnoninferiority = 0.005). No difference was found in the incidence of treatment-related adverse events. Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients. This trial was registered at ClinicalTrials.gov as #NCT03384277.

Application of dose-gradient function in reducing radiation induced lung injury in breast cancer radiotherapy.

OBJECTIVE: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy. MATERIALS AND METHODS: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as DGH=VDVp3, then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction. The dosimetric parameters of target area and organs at risk in 30 cases before and after re-optimization were compared. RESULTS: On the premise of ensuring that the target dose met the clinical requirements, the trigger factor obtained based on DGF could further reduce the V5, V10, V20, V30 and mean lung dose (MLD) of the ipsilateral lung in breast cancer radiotherapy, P < 0.01. And the D2cc and mean heart dose (MHD) of the heart were also reduced, P < 0.01. Besides, the NTCPs of the ipsilateral lung and the heart were also reduced, P < 0.01. CONCLUSION: The trigger factor obtained based on DGF is efficient in reducing radiation induced lung injury in breast cancer radiotherapy.

A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy.

AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100 mg, cetagliptin 50 mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50 mg and placebo were switched to cetagliptin 100 mg for 28 weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24 weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17 ± 0.794%, -1.23 ± 0.896% in cetagliptin 100 mg and 50 mg plus metformin group, respectively. No difference was observed between the cetagliptin 100 mg and 50 mg plus metformin group. Patients with higher baseline HbA1c levels (≥8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100 mg (49.4%) and cetagliptin 50 mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment ß-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.

The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.

BACKGROUND: Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease. High thrombus burden is an independent risk factor for poor prognosis of acute myocardial infarction. However, there is no study on the correlation between soluble semaphorin 4D (sSema4D) level and high thrombus burden in patients with STEMI. PURPOSE: This study aimed to investigate the relationship between sSema4D level and the thrombus burden of STEMI and further explore its effect on the main predictive value of the occurrence of major adverse cardiovascular events (MACE). METHODS: From October 2020 to June 2021, 100 patients with STEMI diagnosed in our hospital's cardiology department were selected. According to the thrombolysis in myocardial infarction(TIMI)score, STEMI patients were divided into high thrombus burden groups (55 cases) and non-high thrombus burden groups (45 cases) 0.74 patients with stable coronary heart disease (CHD) were selected as stable CHD group, and 75 patients with negative coronary angiography (CAG) were selected as control group. Serum sSema4D levels were measured in 4 groups. The correlation between serum sSema4D and high-sensitivity C-reactive protein (hs-CRP) in patients with STEMI was analyzed. The relationship of serum sSema4D levels between the high and non-high thrombus burden group was evaluated. The effect of sSema4D levels on the occurrence of MACE was explored in one year after percutaneous coronary intervention. RESULTS: Serum sSema4D level was positively correlated with hs-CRP level in STEMI patients (P < 0.05) with a correlation coefficient of 0.493. The sSema4D level was significantly higher in the high versus non-high thrombus burden group (22.54(20.82,24.17), P < 0.05). Moreover, MACE occurred in 19 cases in high thrombus burden group and 3 cases in non-high thrombus burden group. The results of Cox regression analysis showed that sSema4D was an independent predictor of MACE (OR = 1.497,95% CI: 1.213-1.847, P < 0.001). CONCLUSION: The sSema4D level is associated with coronary thrombus burden and is an independent risk factor for MACE.

Managing admission and discharge processes in intensive care units.

The intensive care unit (ICU) is one of the most crucial and expensive resources in a health care system. While high fixed costs usually lead to tight capacities, shortages have severe consequences. Thus, various challenging issues exist: When should an ICU admit or reject arriving patients in general? Should ICUs always be able to admit critical patients or rather focus on high utilization? On an operational level, both admission control of arriving patients and demand-driven early discharge of currently residing patients are decision variables and should be considered simultaneously. This paper discusses the trade-off between medical and monetary goals when managing intensive care units by modeling the problem as a Markov decision process. Intuitive, myopic rule mimicking decision-making in practice is applied as a benchmark. In a numerical study based on real-world data, we demonstrate that the medical results deteriorate dramatically when focusing on monetary goals only, and vice versa. Using our model, we illustrate the trade-off along an efficiency frontier that accounts for all combinations of medical and monetary goals. Coming from a solution that optimizes monetary costs, a significant reduction of expected mortality can be achieved at little additional monetary cost.

A quality improvement project to reduce postoperative adverse respiratory events and increase safety in the postanesthesia care unit of a pediatric institution.

BACKGROUND: Quality improvement methods can identify solutions and make dramatic improvements in patient safety during daily clinical care. The science of quality improvement in healthcare is still a very new concept in developing countries like China. AIMS: We initiated a quality improvement project to minimize adverse respiratory events in our postanesthesia care unit with the guidance of an experienced quality improvement expert from Cincinnati Children's Hospital Medical Center. METHODS: We set up a quality improvement team that included anesthesia safety team members at Shanghai Children's Medical Center, and a quality improvement expert in pediatric anesthesia from Cincinnati Children's Hospital Medical Center. Data from the previous year were reviewed. After using Failure Mode and Effect Analysis to access risks associated with the current process, a Key Driver Diagram and a Smart Aim were developed. Key drivers included establishing a safety culture, resource allocation to meet needs, education and training, standardization of care, improved communication and handoff, and enhanced detection, recognition, and response to adverse events. Using Plan-Do-Study-Act cycles of the improvement model, interventions were conducted to improve the process. The primary outcome was the percentage of postoperative respiratory adverse events in the postanesthesia care unit, and we calculated the average recovery time as a balancing measure. Data were collected and analyzed using a run chart and control chart. RESULTS: The median percentage of respiratory adverse events in postanesthesia care unit decreased from 2.8% to 1.4%. Respiratory adverse events were reduced by over 30% compared to the previous period with no significant change in mean recovery time. CONCLUSION: Using quality improvement methods, we successfully reduced the percentage of respiratory adverse events in the postanesthesia care unit. This helped to establish a safety culture among the anesthesia staff. Quality and safety improvement can be successfully implemented in developing countries like China with collaboration with quality improvement experts from more experienced institutions.

Application research on reducing radiation-induced lung injury with a trigger operator based on overlap volume histogram (OVH) in breast cancer postoperative radiotherapy.

This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P < 0.01), and in the V5, V10, V20, V30, and V40 of the L-Lung in the SG (P < 0.01). Our findings suggest that the proposed trigger operator can improve plan quality, thereby reducing radiation-induced lung injury in postoperative radiotherapy for breast cancer.

Lung ultrasound evaluation of incremental PEEP recruitment maneuver in children undergoing cardiac surgery.

AIM: To explore the effect of incremental positive end-expiratory pressure recruitment maneuver (iPEEPRM) in children with congenital heart diseases (CHDs) using lung ultrasound. METHODS: Thirty-six children aged 3 months to 5 years scheduled for cardiac surgery participated. iPEEPRM was performed with PEEP stepwise increase (0-5-10-15 cmH2 O) and decrease at the same rate before and after surgery. Atelectatic areas, ultrasound scores, arterial oxygen pressure (PaO2 ), and respiratory system dynamic compliance per kilogram body weight (CDyn/kg) were analyzed before and after iPEEPRM. The primary outcome is the incidence of atelectasis. Secondary outcomes are oxygenation, ventilation, CDyn/kg, and atelectasis area. RESULTS: iPEEPRM was successfully applied in 92% (33/36) children before surgery and 71% (24/34) children after surgery. The incidence of atelectasis was significantly reduced by iPEEPRM from 76% to 15% before surgery and from 92% to 38% after surgery, respectively (P < .001). Before surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 32.5 (0-128.1) mm2 vs 0 (0-0) mm2 and 8 (3-12) vs 2 (0-4). PaO2 and CDyn/kg were significantly increased after iPEEPRM: 243 (129-275) mm Hg vs 278 (207-323) mm Hg and 0.6 (0.4-0.7) mL/cmH2 O/kg vs 0.8 (0.6-1.0) mL/cmH2 O/kg. After surgery, iPEEPRM significantly reduced atelectatic areas and ultrasound scores: 45.7 (13.1-115.8) mm2 vs 0 (0-34.7) mm2 , and 9 (6-12) vs 3 (0-5). PaO2 and CDyn/kg were also significantly increased after iPEEPRM. CONCLUSIONS: iPEEPRM effectively reduced atelectasis, improved lung aeration, oxygenation, and CDyn/kg in children undergoing cardiac surgery.